title: Role of protein kinase C phosphorylation in rapid desensitization of metabotropic glutamate receptor 5.
abstract: Metabotropic glutamate receptors (mGluRs) coupled to phosphoinositide hydrolysis desensitize in response to prolonged or repeated agonist exposure, and evidence suggests that this involves activation of protein kinase C (PKC). The present studies were undertaken to determine if cloned mGluR5 undergoes similar PKC-mediated desensitization and to investigate the molecular mechanism underlying PKC-induced desensitization. In Xenopus oocytes, both mGluR5a and mGluR5b showed pronounced desensitization in response to a brief activation by glutamate. Pharmacological studies clearly suggest that this desensitization requires PKC-mediated phosphorylation. Analysis of PKC consensus phosphorylation site mutants suggests that PKC phosphorylates mGluR5 at multiple sites to induce a relatively rapid form of desensitization. Because mGluRs play important roles in synaptic plasticity and in excitotoxicity, this desensitization may be involved in the dynamic regulation of these processes.
authors.affiliation: Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Gereau
authors.forename: S F
authors.initials: SF
authors.lastname: Heinemann
mesh_terms: D000818:Animals; D005260:Female; D009865:Oocytes / Q000378:metabolism; D010766:Phosphorylation; D017354:Point Mutation; D011493:Protein Kinase C / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D014981:Xenopus
chemical_list: D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D011493:Protein Kinase C